RESUMO
A phase I clinical trial was performed to examine the safety and immunogenicity of a multi-epitope polypeptide comprising the central 15 amino acids of the V3 loop from six HIV-1 isolates. This protein called TAB9 was emulsified in Montanide ISA720 (Seppic, Paris) and administered intramuscularly at doses of 0, 0.2 and 1 mg to 24 healthy, HIV-1 seronegative adult males. Three immunisations were given at months 0, 1 and 6 in a randomised, double blind, placebo controlled clinical trial. The placebo was generally well tolerated. However, severe local reactions were observed in TAB9 vaccinated subjects after the second and third inoculations. Seven out of eight volunteers from the lower dose group showed moderate or severe local inflammation, while four out of eight subjects from the higher dose group developed granulomas and sterile abscesses. In general, the reactogenicity depended on the number of inoculations given and the dose of TAB9. Both doses were immunogenic, all immunised volunteers seroconverted and antibodies were broadly reactive against the V3 peptides included in the protein. All vaccine's sera reacted against gp120 in Western blot and 50% of them also neutralised at least one out of five laboratory isolates tested. No differences between doses were found. Anti TAB9 lymphoproliferative responses were observed, being more intense in the high dose group. Due to the strong local reactions that were found in this study, a change in the formulation will be required for further trials with this vaccine candidate in humans.
Assuntos
Vacinas contra a AIDS/imunologia , Adjuvantes Imunológicos/administração & dosagem , Epitopos/imunologia , HIV-1/imunologia , Manitol/administração & dosagem , Ácidos Oleicos/administração & dosagem , Adulto , Sequência de Aminoácidos , Western Blotting , Ensaio de Imunoadsorção Enzimática , Epitopos/administração & dosagem , Anticorpos Anti-HIV/sangue , Humanos , Ativação Linfocitária , Masculino , Manitol/análogos & derivados , Dados de Sequência MolecularRESUMO
Current chemotherapy for the treatment of infections caused by the liver fluke Fasciola hepatica is not satisfactory. Therefore, the efficacy and tolerability of triclabendazole (TCZ) was assessed for this indication. Eighty-two patients (51 female, 31 male, age 15-81 yr, mean 42 yr) with chronic or latent F. hepatica infection refractory to previous anti-helminthic chemotherapy were enrolled in a 60-day open, non-comparative trial. Patients received 20 mg/kg TCZ as two doses of 10 mg/kg administered after food 12 hr apart. Efficacy of treatment was assessed by stool microscopy, determination of Fasciola excretory-secretory antigen (FES) in feces, and by ultrasonography (US) which were systematically performed pre-therapy and on Days 1-7, 15, 30, and 60 post-therapy. For continuous safety assessment, patients were hospitalized during the first week after therapy and then monitored at home for the appearance of any adverse events. Clinical chemistry and hematology tests were carried out on Days 1, 3, 7, 15, and 60, and whenever an adverse effect occurred possibly related to therapy. Seventy-one (92.2%) of the 77 patients who completed the 60-day follow-up period became egg-negative. Efficacy of therapy was supported by the disappearance or decrease of FES antigen and of ultrasonography abnormalities. In the 6 remaining patients, parasitological cure was achieved by another single TCZ dose of 10 mg/kg on Day 60. A total of 74 adverse events possibly related to therapy was reported by 54 patients. The most important adverse event was colic-like abdominal pain (40 patients [49%]) consistent with the expulsion of the parasite through the bile ducts as confirmed by US on Days 2-7. Most adverse events (53) were graded as mild, 20 as moderate, and only 1 as severe (a biliary colic responding to spasmolytic therapy within two hours). Triclabendazole 20 mg/kg is an effective therapy for the treatment of F. hepatica infection in patients who have failed to respond to other antihelminthic agents. Biliary colics reflecting the expulsion of dead or damaged parasites usually occur during Day 3-7 and respond well to spasmolytic therapy.
Assuntos
Anti-Helmínticos/uso terapêutico , Anticorpos Anti-Helmínticos/sangue , Benzimidazóis/uso terapêutico , Fasciola hepatica/imunologia , Fasciolíase/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Doença Crônica , Cuba , Fasciola hepatica/isolamento & purificação , Fasciolíase/diagnóstico por imagem , Fezes/parasitologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Triclabendazol , UltrassonografiaRESUMO
Three acyclovir resistant strains of HSV-2 were isolated from mucoulcerative lesions in a patient suffering from AIDS in whom the oral and intravenous acyclovir treatment was unsuccessful. All the isolates were classified by monoclonal antibodies and showed no differences in DNA restriction patterns.